This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CLC chloride-transport proteins are expressed ubiquitously. CLC proteins play central roles in neuronal, muscular, cardiovascular, and epithelial function. Because of these vital physiological roles, many are potential drug targets for treating human disease. Defects in these proteins are responsible for human diseases of kidney and bone, for disorders of blood-pressure regulation, and for epilepsy. Research in the Maduke lab involves a combination of electrophysiological, structural, and biochemical methods. The current study utilizes structural information to understand the mechanism of CLC inhibition. Studies will include inhibitors.